DESCRIPTION: We are requesting the acquisition of a Keyence BZ-X700 All-In-One Automated Imaging System with Multi-Stack Module to be centrally housed in the San Diego VAMC and to be available without fee to all VA researchers. This fully-automated instrument is capable of confocal-like multi-stack imaging and real-time focusing of thick tissue sections, rapid automatic high-magnification image acquisition and stitching of composite images, and three-dimensional profiling of serial tissue sections imaged at high resolution. The control software is simple and intuitive, and thus with minimal training a novice user can scan a series of tissue sections from an entire organ, generate high-resolution composites of each tissue section, and merge all composites into a single three-dimensional rendering of the entire tissue. Traditional microscopes available at the San Diego VAMC and neighboring institutions do not possess these capabilities. Generating similar data with traditional microscopes is difficult and time-consuming, requiring roughly 10 times more work hours and extensive training. Due to the considerable reduction of work hours when compared to traditional microscopes, as well as the widespread use of histology among VA researchers, we expect the device to fully pay for itself within the first year of service. The instrument is completely enclosed with minimal moving parts, and includes self-calibrating optics and an internally self-aligning light train. This both increass ease of operation and reduces the need for routine maintenance. The Keyence corporation does not require a maintenance contract and will support the device for its entire lifetime. Due to its ease of use and minimal maintenance, the BZ-X700 will not require any operational costs beyond the initial purchase, and thus no fee will be charged for its use. Furthermore, because the device is fully enclosed, it does not require a darkroom and can be housed centrally within the main research facility of the San Diego VAMC. These features will enable a wide range of VA researchers to benefit from the device's unique capabilities. Imaging and analysis of histological tissue sections is a widespread technique, and the requesting scientists represent a variety of disciplines including neuroscience, cardiology, and general surgery. The requesting scientists investigate a broad range of translational therapies with substantial benefit for veterans, including therapies for neurodegenerative disease such as Alzheimer's disease and amyotrophic lateral sclerosis, chronic spinal cord injury, otologic disorders, hearing loss, traumatic brain injury, glaucoma, macular degeneration, Retinitis Pigmentosa, Usher syndrome, stroke, ischemic heart disease, and congestive heart failure. In addition, due to the power, ease of use, speed of image acquisition, and flexibility of the BZ-X700, we expect the system to attract and accommodate a large number of VA researchers beyond the requesting scientists, expanding its benefit to an even broader range of translational research. The BZ-X700 will thus have a substantial impact on many projects, reducing the number of work hours that are required for high-magnification imaging of histological tissue sections, generating higher quality images for presentation and analysis, and enabling researchers to quickly and easily produce 3D reconstructions of whole tissues. This instrument will therefore provide a major contribution to the VA's long-term research goals, impacting a wide range of translational research at the San Diego VAMC by reducing overall costs for tissue processing and speeding the development of many critical therapies.